Our long term goal is to understand the regulatory mechanisms of carbohydrate metabolism in various mammalian tissues. Specifically, we are interested in the regulation of phosphofructokinase, one of the key regulatory enzymes of glycolysis. In 1980, we and two other groups discovered the most potent activator of phosphofructokinase, fructose 2,6-P2, in liver. Subsequently, this activator is found to occur in all mammalian tissues, in plants, and yeast and thus stimulated a new investigation into the roles of fructose 2,6-P2 in regulation of glycolysis in these cells. It plays an important role in dietary and hormonal regulation of glucose homeostasis in liver. It also is important in stimulation of glycolysis in working heart and under epinephrine and insulin stimulation. Our current objective is to determine its role in liver under ischemic conditions, since we found that the fructose 2,6-P2 level change within a few seconds and continue to oscillate for 2 min. We continue to investigate the biochemical mechanism for this interesting observation. We are also investigating the structure and function of various Fru 6-P,2-kinase:Fru 2,6-Pase isozymes which catalyze the synthesis and degradation of Fru 2,6-P2. These studies will help in our understanding of how carbohydrate metabolism is regulated in various mammalian tissues.